Drug specific resistance to oxaliplatin is associated with apoptosis defect in a cellular model of colon carcinoma
Drug specific resistance to oxaliplatin is associated with apoptosis defect in a cellular model of colon carcinoma
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DOI：
10.1016/s0014-5793(02)03347-1
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发表时间：
2002-10-09
期刊：
影响因子：
3.5
通讯作者：
Pau, B
中科院分区：
文献类型：
--
作者：
Gourdier, I;Del Rio, M;Pau, B
为了研究对奥沙利铂的获得性耐药性，我们从HCT 116细胞系中选择了两个耐药克隆。我们发现，耐药表型与奥沙利铂诱导的细胞凋亡的耐药性相关，如通过流式细胞仪分析和半胱天冬酶3激活的蛋白质印迹法所证明的。此外，耐药表型显示出伴随的耐氯尼达明和三氧化二砷，这是线粒体凋亡的诱导剂。此外，在最耐药的克隆中观察到由于移码突变导致的Bax表达的完全丧失。总之，这些发现表明，改变的细胞介导的细胞凋亡可能在奥沙利铂耐药中发挥作用。(C)2002年欧洲生物化学学会联合会。由Elsevier Science B.V.出版，版权所有。
To investigate acquired resistance to oxaliplatin, we selected two resistant clones from the HCT116 cell line. We found that the resistant phenotype was associated with resistance to oxaliplatin-induced apoptosis as demonstrated by FACS analysis and by Western blotting of caspase 3 activation. In addition, the resistant phenotype showed a concomitant resistance to lonidamine and arsenic trioxide which are inducers of mitochondrial apoptosis. Furthermore, a complete loss of Bax expression due to a frameshift mutation was observed in the most resistant clone. Taken together, these findings suggest that altered mitochondrial-mediated apoptosis could play a role in oxaliplatin resistance. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.